The second revision of the “Guideline for Elemental Impurities Q3D(R2)” has achieved “step 4” (adoption by the Regulatory Members of the ICH Assembly) on April 26, 2022 and is available on the ICH website.

Compared with the draft dated September 2020, the final version of this second revision includes some revisions and adaptations:

§  Appendix 2: Established PDEs for Elemental Impurities PDEs (Permitted Daily Exposure) values for Gold, Silver and Nickel have been adjusted

§  Appendix 3: Individual Safety Assessments Gold and Silver monographs were revised

§  Appendix 5: Limits for Elemental Impurities by the Cutaneous and Transcutaneous Route was added in the second revision of the guideline and contains information on the limits for impurities for cutaneously or transcutaneously applied medicinal products.

The appendix focuses on the forms of impurities most likely to be detected following the application of pharmaceuticals to human skin. It also considers both local and systemic toxicities.

“[…] ICH decided to adopt a “generic approach” instead of an element-by-element one.

The reason for the choice is due to the results of the studies consulted. Indeed, these would tend to report a “disappearance” of impurities in the skin rather than transcutaneous absorption.”

The “Harmonized Guideline for Elemental Impurities Q3D(R2)” can be found on the ICH website.